淋巴细胞指标在新型冠状病毒肺炎诊治中的作用

doi:10.3877/cma.j.issn.2095-5820.2021.03.009

目前新型冠状病毒(SARS-CoV-2)在全球范围内的传播对世界公共健康构成了巨大威胁。SARS-CoV-2实验室检测对疾病的诊断和预防起着重要作用。本文通过文献检索和数据收集、归纳、分析，阐述实验室常用的淋巴细胞指标(如淋巴细胞计数LYMPH、淋巴细胞百分比LYMPH%、中性粒细胞和淋巴细胞的比值NLR、淋巴细胞亚群等)对新型冠状病毒感染辅助诊断、预后评估、疗效监测的作用，为新型冠状病毒肺炎(COVID-19)的治疗及预后判断提供参考依据。

关键词: 冠状病毒科, 淋巴细胞

At present, the global spread of novel coronavirus (SARS-CoV-2) has posed a great threat to world public health. SARS-CoV-2 laboratory testing plays an important role in the diagnosis and prevention of disease. Through literature retrieval, data collection, analysis and induction, the role of commonly used lymphocyte indicators was elaborated in auxiliary diagnosis, prognosis assessment and efficacy monitoring of novel coronavirus infection, so as to provide reference for the treatment, prevention and control of COVID-19.

Key words: Coronaviridae, Lymphocyte

表1 COVID-19患者白细胞各指标水平［M(P25，P75)］

项目	作者	总体	非重症	重症	P值
WBC×10⁹/L	Qin^［8］	5.3(3.9~7.5)	4.9(3.7~6.1)	5.6(4.3~8.4)	＜0.001
	He^［16］	4.75(3.98~5.94)	4.74(4.04~5.76)	4.84(3.83~7.85)	0.021
	Zhu^［17］	5.00(4.20~6.80)	5.00(4.30~6.50)	5.35(4.13~7.53)	0.568
NEUT×10⁹/L	Qin^［8］	3.9(2.6~5.8)	3.2(2.1~4.4)	4.3(2.9~7.0)	＜0.001
	Liu^［18］	3.6(2.5~6.4)	3.1 (2.2~4.4)	6.7 (3.9~10.5)	＜0.001
	Zhu^［17］	3.37(2.54~4.55)	3.29(2.54~4.40)	3.89(2.25~6.57)	0.309
LYMPH×10⁹/L	Qin^［8］	0.9(0.6~1.2)	1.0(0.7~1.3)	0.8(0.6~1.1)	＜0.001
	Liu^［18］	0.97(0.65~1.42)	1.17(0.89~1.58)	0.60(0.38~0.76)	＜0.001
	Zhu^［17］	1.21(0.87~1.48)	1.23(0.90~1.53)	0.74(0.47~1.18)	0.004
NLR	Qin^［8］	4.2(2.5~7.7)	3.2(1.8~4.9)	5.5(3.3~10.0)	＜0.001
	Liu^［18］	3.6 (2.0~9.7)	2.6 (1.7~4.5)	10.4 (7.2~21.3)	＜0.001
	Zhu^［17］	2.91(1.95~4.15)	2.75(1.90~3.95)	4.24(3.00~10.87)	0.015

表1 COVID-19患者白细胞各指标水平［M(P25，P75)］

项目	作者	总体	非重症	重症	P值
WBC×10⁹/L	Qin^［8］	5.3(3.9~7.5)	4.9(3.7~6.1)	5.6(4.3~8.4)	＜0.001
	He^［16］	4.75(3.98~5.94)	4.74(4.04~5.76)	4.84(3.83~7.85)	0.021
	Zhu^［17］	5.00(4.20~6.80)	5.00(4.30~6.50)	5.35(4.13~7.53)	0.568
NEUT×10⁹/L	Qin^［8］	3.9(2.6~5.8)	3.2(2.1~4.4)	4.3(2.9~7.0)	＜0.001
	Liu^［18］	3.6(2.5~6.4)	3.1 (2.2~4.4)	6.7 (3.9~10.5)	＜0.001
	Zhu^［17］	3.37(2.54~4.55)	3.29(2.54~4.40)	3.89(2.25~6.57)	0.309
LYMPH×10⁹/L	Qin^［8］	0.9(0.6~1.2)	1.0(0.7~1.3)	0.8(0.6~1.1)	＜0.001
	Liu^［18］	0.97(0.65~1.42)	1.17(0.89~1.58)	0.60(0.38~0.76)	＜0.001
	Zhu^［17］	1.21(0.87~1.48)	1.23(0.90~1.53)	0.74(0.47~1.18)	0.004
NLR	Qin^［8］	4.2(2.5~7.7)	3.2(1.8~4.9)	5.5(3.3~10.0)	＜0.001
	Liu^［18］	3.6 (2.0~9.7)	2.6 (1.7~4.5)	10.4 (7.2~21.3)	＜0.001
	Zhu^［17］	2.91(1.95~4.15)	2.75(1.90~3.95)	4.24(3.00~10.87)	0.015

图1 重症和非重症COVID-19患者淋巴细胞降低百分比

图2 不同NLR值COVID-19患者存活和死亡百分比

表2 COVID-19患者淋巴细胞亚群水平［M(P25，P75)］

指标	作者	总体	非重症	重症	P值
CD3⁺/L	He^［16］	801 (496~1154)	1 066(804~1321)	305(198~525)	＜0.001
	Kong^［20］	700(400~1000)	900(600~1300)	500(300~700)	＜0.001
CD4⁺/L	He^［16］	461 (269~701)	645 (461~794)	184(103~293)	＜0.001
	Kong^［20］	400(200~600)	500(300~800)	200(100~400)	＜0.001
CD8⁺/L	He^［16］	291 (164~424)	366 (274~482)	121 (54~197)	＜0.001
	Kong^［20］	200(100~400)	300(200~500)	200(100~300)	＜0.001
CD4⁺/CD8⁺	He^［16］	1.66(1.27~2.20)	1.66 (1.37~2.16)	1.57(1.10~2.36)	0.342
	Kong^［20］	1.8(0.9~2.9)	0.2 (1~1.1)	1.5 (0.7-2.3)	0.030
CD19⁺/L	He^［16］	155 (105~229)	190 (139~268)	91 (54~139)	＜0.001
	Kong^［20］	100(100~200)	100(100~200)	100(50~100)	0.082
CD16⁺CD56⁺/L	He^［16］	127 (81~209)	144 (93~231)	105 (66~168)	＜0.001
	Kong^［20］	100(100~200)	200(100~300)	100(100~200)	0.074

表2 COVID-19患者淋巴细胞亚群水平［M(P25，P75)］

指标	作者	总体	非重症	重症	P值
CD3⁺/L	He^［16］	801 (496~1154)	1 066(804~1321)	305(198~525)	＜0.001
	Kong^［20］	700(400~1000)	900(600~1300)	500(300~700)	＜0.001
CD4⁺/L	He^［16］	461 (269~701)	645 (461~794)	184(103~293)	＜0.001
	Kong^［20］	400(200~600)	500(300~800)	200(100~400)	＜0.001
CD8⁺/L	He^［16］	291 (164~424)	366 (274~482)	121 (54~197)	＜0.001
	Kong^［20］	200(100~400)	300(200~500)	200(100~300)	＜0.001
CD4⁺/CD8⁺	He^［16］	1.66(1.27~2.20)	1.66 (1.37~2.16)	1.57(1.10~2.36)	0.342
	Kong^［20］	1.8(0.9~2.9)	0.2 (1~1.1)	1.5 (0.7-2.3)	0.030
CD19⁺/L	He^［16］	155 (105~229)	190 (139~268)	91 (54~139)	＜0.001
	Kong^［20］	100(100~200)	100(100~200)	100(50~100)	0.082
CD16⁺CD56⁺/L	He^［16］	127 (81~209)	144 (93~231)	105 (66~168)	＜0.001
	Kong^［20］	100(100~200)	200(100~300)	100(100~200)	0.074

图3 轻症和重症COVID-19患者淋巴亚群降低百分比

1	Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China[J]. Lancet, 2020, 395:497-506.
2	Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome[J]. Lancet Respir Med, 2020, 8:420-422.
3	Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses[J]. Nat Rev Microbiol, 2019,17:181-192.
4	Su S, Wong G, Shi W, et al. Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses[J]. Trends Microbiol, 2016,24:490-502.
5	Xiaolu Tang, Changcheng W, Xiang L, et al. On the origin and continuing evolution of SARS-CoV-2[J]. Natl Sci Rev, 2020, 7(6): 1012-1023.
6	Kam K, Yung CF, Cui L, et al. A Well Infant With Coronavirus Disease 2019 With High Viral Load[J]. Clin Infect Dis, 2020,71:847-849.
7	Li R, Pei S, Chen B, et al. Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2)[J]. Science, 2020,368:489-493.
8	Qin C, Zhou L, Hu Z, et al. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China[J]. Clin Infect Dis, 2020,71:762-768.
9	Tan M, Liu Y, Zhou R, et al. Immunopathological characteristics of coronavirus disease 2019 cases in Guangzhou, China[J]. Immunology, 2020,160:261-268.
10	Zhang B, Zhou X, Zhu C, et al. Immune phenotyping based on the neutrophil-to-lymphocyte ratio and igg level predicts disease severity and outcome for patients with COVID-19[J]. medRxiv, 2020,7:157.
11	Chen XP, Ling JX, Mo PZ, et al. Restoration of leukomonocyte counts is associated with viral clearance in COVID-19 hospitalized patients[J]. medRxiv, 2020: 20030437.
12	Guan WJ, Ni ZY, Hu Y. Clinical characteristics of coronavirus disease 2019 in China[J]. N Engl J Med, 2020, 382:1708-1720.
13	Wan Y, Shang J, Graham R, et al. Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus[J]. J Virol , 2020, 94(7): e00127-20.
14	Sun S, Cai X, Wang H, et al. Abnormalities of peripheral blood system in patients with COVID-19 in Wenzhou, China[J]. Clinica chimica acta, 2020, 507:174-180.
15	安艳晓, 柳克晔, 王洋, 等. 中性粒细胞与淋巴细胞比值和非瓣膜性房颤患者左房血栓之间的关系研究[J]. 医学研究与教育, 2014, 31:34-37.
16	He R, Lu Z, Zhang L, et al. The clinical course and its correlated immune status in COVID-19 pneumonia[J]. J Clin Virol, 2020,127:104361.
17	Zhu Z, Cai T, Fan L, et al. Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019[J]. Int J Infect Dis, 2020, 95:332-339.
18	陈星, 区静怡, 黄颖, 等. 多种血液学指标在新型冠状病毒肺炎中的诊断价值[J]. 检验医学, 2020, 35(4):295-299.
19	Zhang G, Hu C, Luo L, et al. Clinical features and outcomes of 221 patients with COVID-19 in Wuhan, China[J]. J Clin Virol, 2020:104364-104364.
20	Kong M, Zhang H, Cao X, et al. Higher level of neutrophil-to-lymphocyte is associated with severe COVID-19[J]. Epidemol Infect, 2020, 148:e139.
21	Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study[J]. Lancet, 2020, 395:507-513.
22	Guan WJ, Ni ZY, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China[J]. N Engl J Med, 2020, 382(18):1708-1720.
23	靳云洲, 李明芳, 郑胜, 等. 248例新型冠状病毒肺炎患者血常规及心肌酶谱分析[J]. 实用临床医药杂志, 2020:1-4.
24	Liu L, Zheng Y, Cai L, et al. Neutrophil‐to‐lymphocyte ratio, a critical predictor for assessment of disease severity in patients with COVID‐19[J]. Int J Lab Hematol, 2021, 43(2): 329-335.
25	Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China[J]. Jama, 2020, 323(11):1061-1069.
26	Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study[J]. Lancet, 2020, 395(10229): 1054-1062.
27	Liu Y, Du X, Chen J, et al. Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19[J]. J Infect, 2020, 81(1):e6-e12.
28	Liu J, Liu Y, Xiang P, et al. Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage[J]. J Transl Med, 2020, 18:206.
29	Kasama T, Miwa Y, Isozaki T, et al. Neutrophil-derived cytokines: potential therapeutic targets in inflammation[J]. Curr Drug Targets Inflamm Allergy, 2005, 4:273-279.
30	Celikbilek A, Ismailogullari S, Zararsiz G. Neutrophil to lymphocyte ratio predicts poor prognosis in ischemic cerebrovascular disease[J]. J Clin Lab Anal, 2014, 28:27-31.
31	Zheng YS, Huang Z, Ying GP, et al. Study of the lymphocyte change between COVID-19 and non-COVID-19 pneumonia cases suggesting other factors besides uncontrolled inflammation contributed to multi-organ injury[J]. medRxiv, 2020: 20024885.
32	靳云洲, 李明芳, 郑胜, 等. 渝东北片区新型冠状病毒肺炎患者不同病情状态下淋巴细胞、白细胞介素-6及炎症指标的变化[J]. 实用临床医药杂志, 2020:1-4.
33	Liao MF, Liu Y, Yuan J, et al. The landscape of lung bronchoalveolar immune cells in COVID-19 revealed by single-cell RNA sequencing[J]. medRxiv, 2020: 20026690.
34	张益明, 高世定, 王占科, 等. 3例新型冠状病毒肺炎患者外周血CD4+T淋巴细胞和CD4+/CD8+比值变化[J]. 国际检验医学杂志, 2020, 17:2173-2176.
35	Meckiff BJ, Ramirez-Suastegui C, Fajardo V, et al. Imbalance of regulatory and cytotoxic SARS-CoV-2-reactive CD4(+) T cells in COVID-19[J]. Cell, 2020, 183:1340-1353.
36	Roncati L, Nasillo V, Lusenti B, et al. Signals of Th2 immune response from COVID-19 patients requiring intensive care[J]. Ann Hematol, 2020, 99:1419-1420.
37	李国华, 李玲, 何敏, 等. 多种炎症指标联合淋巴细胞亚群在COVID-19不同临床分型的临床诊断价值分析[J]. 重庆医科大学学报, 2020, 45:971-975.
38	包芳, 史尉利, 胡静, 等. 新型冠状病毒肺炎淋巴细胞亚群与严重程度的相关分析[J]. 北京大学学报(医学版), 2020, 52:1075-1081.
39	Osakwe CE, Bleotu C, Chifiriuc MC, et al. TH1/TH2cytokine levels as an indicator for disease progression in human immunodeficiency virus type 1 infection and response to antiretroviral therapy[J]. Roum Arch Microbiol Immunol, 2010, 69:24-34.
40	陈丹龙, 杨芳, 罗志英, 等. 全球抗新型冠状病毒药物研发现状和瓶颈[J]. 中国药理学通报, 2020, 36:459-469.

[1]	王亚萍, 樊菁, 侯牛牛, 凌瑞. 肿瘤浸润性淋巴细胞在HER-2阳性早期乳腺癌中的临床意义[J]. 中华乳腺病杂志(电子版), 2023, 17(04): 203-209.
[2]	罗晨, 宗开灿, 李世颖, 傅应亚. 微小RNA-199a-3p调控CD4^＋T细胞表达参与肺炎支原体肺炎患儿免疫反应研究[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 569-574.
[3]	韩春颖, 王婷婷, 李艳艳, 朴金霞. 子宫内膜癌患者淋巴管间隙浸润预测因素研究现状[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(04): 403-409.
[4]	崔键, 戴庆. 基于肝囊型包虫病所致过敏反应模型研究Treg细胞数量比例与过敏反应的关系[J]. 中华普外科手术学杂志(电子版), 2023, 17(04): 427-430.
[5]	孟锦雯, 刘治坤, 顾钰峰, 王建国, 杨帆, 郑树森, 徐骁. 基于卷积神经网络的肝细胞癌复发预警数字病理学模型研究[J]. 中华肝脏外科手术学电子杂志, 2023, 12(03): 272-277.
[6]	于小鹏, 陈晨, 陈家璐, 童焕军, 邱应和, 吴泓, 宋天强, 何宇, 毛先海, 翟文龙, 程张军, 李敬东, 耿智敏, 汤朝晖. 肝内胆管细胞癌淋巴结清扫患者生存获益的术前临床病理特征[J]. 中华肝脏外科手术学电子杂志, 2023, 12(03): 278-283.
[7]	王娟, 高俊, 周伊兰, 李小红, 史兵伟, 潘美珍. 血清IL-2、IL-17和骨密度关系及其对骨质疏松症的预测价值[J]. 中华老年骨科与康复电子杂志, 2023, 09(05): 295-300.
[8]	陈科春, 吴秋义, 李建, 周寅, 徐周. 基于不同中性粒细胞与淋巴细胞比值探讨机械取栓术后首次CT征象与患者预后的关系[J]. 中华脑科疾病与康复杂志(电子版), 2023, 13(04): 215-221.
[9]	王庆, 夏婷婷. 未成熟粒细胞计数、C反应蛋白、中性粒细胞/淋巴细胞、降钙素原结合MCTSI评分在急性胆源性胰腺炎中的诊断价值[J]. 中华消化病与影像杂志(电子版), 2023, 13(04): 224-228.
[10]	吴萌, 吴国仲, 王贵红, 端靓靓, 施杰, 王旭, 余婷, 刘伟. IgA肾病患者中性粒细胞-淋巴细胞比值与肾小管萎缩/间质纤维化相关性分析[J]. 中华临床医师杂志(电子版), 2023, 17(9): 972-979.
[11]	符梅沙, 周玉华, 李慧, 薛春颜. 淋巴细胞免疫治疗对复发性流产患者外周血T淋巴细胞亚群分布与PD1/PD-L1表达的影响及意义[J]. 中华临床医师杂志(电子版), 2023, 17(06): 726-730.
[12]	牛文博, 吴凤鹏, 刘月平, 周超熙, 张娟, 胡旭华, 李保坤, 王贵英. 新辅助放化疗对局部进展期直肠癌疗效及肿瘤免疫微环境变化的研究[J]. 中华临床医师杂志(电子版), 2023, 17(05): 519-523.
[13]	吴晓翔, 杨波, 李景漩, 张凤玲, 郭桂辉, 郑少培. 脐动脉超声检查联合NLR、sFlt-1/PLGF对妊娠高血压综合征患者不良妊娠结局的预测价值[J]. 中华临床医师杂志(电子版), 2023, 17(03): 266-271.
[14]	范茹, 刘宇清, 胡晓榕, 王轶奇, 张芬, 岑星, 卜玉洁, 陈俊伟. 系统性红斑狼疮患者长链非编码RNA表达变化及其与CD8⁺T细胞相关性研究[J]. 中华诊断学电子杂志, 2023, 11(03): 184-189.
[15]	刘玉苓, 王婷婷, 吴高峰, 俞淑静. 健康体检人群内脏脂肪面积与新型炎症标志物的相关性研究[J]. 中华肥胖与代谢病电子杂志, 2023, 09(03): 197-202.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

The role of lymphocyte indicators in the diagnosis and treatment of COVID-19

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

The role of lymphocyte indicators in the diagnosis and treatment of COVID-19